tbuckley/cabot-search huggingface dataset:
Abstract MP092: Community-Based, Primary Prevention Programs Decrease the Rate of Metabolic Syndrome in Low Income and Minority Women
Authors: Lauren G Gilstrap, Carina P Fernandez-Golarz, Rajeev Malhotra, Eliana M Pineda, Donna Peltier-Saxe, Catherine Culhane-Herman, Donna Slicis, Malissa J Wood
Journal: Circulation (2012)

Background: Metabolic Syndrome (MetSyn), a composite of waist circumference, blood pressure, triglycerides, HDL and insulin sensitivity, is one of the strongest predictors of type 2 diabetes (DM) and cardiovascular disease (CVD). It is associated with a 4-10 fold increased risk of DM and a 2-3 fold increased risk of CVD. Low income and minority women have some of the highest rates of MetSyn. This study examines the effect of a community based, primary prevention program on the rates of MetSyn in this population. Methods: 64 low income and minority women, with at least two preexisting risk factors, were enrolled in the HAPPY (Health Awareness and Primary Prevention in Your neighborhood) Heart Program in a suburb of Boston. Over this 2 year period, patients were evaluated by an interdisciplinary medical team: their primary physician, cardiologist, nutritionist, physical therapist and health coach. The rate of MetSyn was measured at baseline, year 1 and 2. Comparisons were made either using the paired t test for normally distributed variables or the Wilcoxon Sign test for non-normal variables. Results: We examined the 5 components of the MetSyn individually and the overall MetSyn score (see table). The increase in HDL from baseline to year 1 was not significant, but by year 2, the average HDL had increased from 44.5 to 49.3 (p&lt;0.001). Similarly, by year 2, we observed a decrease of 6.8 mmHg in systolic blood pressure (p=0.05). Finally, by year 2, the average decrease in HbA1c was 0.2 (p&lt;0.001). From baseline to year 1, the average MetSyn score decreased by 0.33 (p=0.017) and by year 2, the improvements were sustained and improved, with an average reduction in score of 0.63 (p&lt;0.001). Conclusion: Our results demonstrate that a comprehensive, lifestyle intervention program is effective at decreasing MetSyn in a high risk minority female population. These improvements may take at least two years to become evident; however, when shepherded by a community based, interdisciplinary team, not only are the improvements significant, they are sustained.
Abstract MP090: “Life’s Simple 7” and Risk of Incident CHD in the REasons for Geographic And Racial Differences (REGARDS) Study
Authors: Monika M Safford, Todd M Brown, Mary Cushman, Christopher Gamboa, Suzanne Judd, Ambar Kulshreshtha, Paul Muntner
Journal: Circulation (2012)

The American Heart Association’s “Life’s Simple 7” (LS7) is a tool intended to encourage improvements in cardiovascular health. It is not clear whether LS7 scores are associated with similar risks for fatal and nonfatal acute coronary heart disease (CHD) events across race-sex groups in the 21st century. REGARDS is following 30,239 community-dwellers age &gt;45 years recruited between 2003-7 from the contiguous US states. Recruitment was designed to balance race and sex; the final sample was 55% female and 41% black. Participants were telephoned every 6 months for cardiovascular disease endpoints, with retrieval of medical records, death certificates, interviews with next-of-kin or proxies, and expert adjudication of endpoints following national consensus recommendations. Acute CHD was defined as definite or probable myocardial infarction (MI) not resulting in death within 28 days (nonfatal acute CHD) or fatal acute CHD. Among participants free of CHD at baseline, we used Cox models to examine hazard ratios for incident overall acute CHD, and, separately, fatal and nonfatal acute CHD for white and black men and women through 2008, examining associations with LS7 score (blood pressure, cholesterol, glucose, body mass index, smoking, physical activity, and diet), each scored as poor (1 point), intermediate (2 points) or ideal (3 points). The score ranged from 7-21 with 21 being the best cardiovascular health. The study sample numbered 24,431 with mean age 64.1 (SD+9.3) years. Mean follow-up over 3.4 (maximum 5.9) years resulted in 515 incident acute CHD events (355 nonfatal, 160 fatal). Race-sex specific hazard ratios for incident acute CHD and incident nonfatal acute CHD per point higher LS7 score are shown in the table. The AHA’s goal of improving cardiovascular health by 20% by 2020 as assessed by LS7 could have major impact on improving CHD outcomes among black and white Americans.
Abstract MP036: The Sex-Specific Association of Fetuin-A with Diabetes in Older Adults: The Rancho Bernardo Study
Authors: Gail A Laughlin, Kevin M Cummins, Christina L Wassel, Elizabeth Barrett-Connor, Joachim H Ix
Journal: Circulation (2012)

Fetuin-A is a hepatic-secretory protein that induces insulin resistance in animals and is elevated in humans with insulin resistance and fatty liver disease. In population-based studies, higher fetuin-A has been shown to predict the development of type 2 diabetes; however, the sex-specific nature of the fetuin-A-diabetes link is unclear. This study tested the hypothesis of a sex-specific association of fetuin-A with prevalent and incident diabetes in a population of 1742 older community-dwelling adults (mean age 71.4 years). Fetuin-A levels (mean, SD in ng/ml) were highest in women using oral estrogen therapy (ET) (55.5, 11.6), intermediate in women not using ET (51.4, 10.2), and lowest in men (50.2, 9.6) (P&lt;.001 for all). At baseline, 14% (n=129) of women and 19% (n=113) of men had prevalent diabetes; during the median 9.1 year follow-up, 32 women and 53 men developed incident diabetes. In combined analyses, there was a significant interaction by sex for the fetuin-A association with both prevalent (P=.007) and incident (P=.020) diabetes. Table 1 presents odds ratios for prevalent diabetes and hazards ratios for incident diabetes per sex-specific SD increase in fetuin-A. Among women, a 1 SD increase in fetuin-A was associated with 79% increased odds of prevalent diabetes and 66% increased risk of incident diabetes adjusting for age and oral ET. Risk estimates for women were only modestly attenuated by additional adjustment for lifestyle, body size, lipids, blood pressure, fasting plasma glucose and insulin resistance. In contrast, among men, although a minor association was suggested in age-adjusted models, risk estimates were attenuated to one in multivariate models. In conclusion, higher fetuin-A levels predict type 2 diabetes in older women independent of established risk factors, but are not related to diabetes risk in older men. Whether these sex-specific associations are relevant to the observation that diabetes is a stronger risk factor for cardiovascular mortality in women than men merits further investigation. Table 1. Odds of Prevalent Diabetes and Risk of Incident Diabetes per SD increase in Fetuin-A Prevalent Diabetes, OR (95% CI) Women (n=1043) Men (n=672) Model 1 1.79 (1.47, 2.17) 1.15 (0.94, 1.41) Model 2 1.69 (1.38, 2.07) 1.14 (0.92, 1.41) Model 3 1.54 (1.25, 1.90) 1.05 (0.83, 1.31) Model 4 1.60 (1.26, 2.03) 1.14 (0.83, 1.56) Model 5 1.54 (1.24, 1.91) 1.02 (0.80, 1.32) Incident Diabetes, HR (95% CI) Women (n=782) Men (n=477) Model 1 1.66 (1.18, 2.34) 1.24 (0.93, 1.65) Model 2 1.64 (1.16, 2.32) 1.12 (0.81, 1.53) Model 3 1.53 (1.04, 2.25) 0.96 (0.69, 1.33) Model 4 1.51 (1.02, 2.23) 0.94 (0.66, 1.34) Model 5 1.51 (1.03, 2.22) 0.91 (0.65, 1.27) Funding(This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont)
Abstract 034: Gestational Diabetes Mellitus Pregnancy is Associated with Subsequent Atherosclerosis in Women During Midlife: CARDIA.
Authors: Erica P Gunderson, Vicky Chiang, Mark J Pletcher, David R Jacobs, Charles P Quesenberry, Stephen Sidney, Cora E Lewis
Journal: Circulation (2012)

Background: Women who develop gestational diabetes mellitus (GDM) during pregnancy have a 7-fold greater risk of type 2 diabetes and 2.5-times greater risk of the metabolic syndrome several years after delivery than women without a history of GDM. Yet, little is known about whether GDM status contributes to early subclinical atherosclerosis after pregnancy. We hypothesize that a history of GDM is a predictor of early atherosclerosis in women during mid-life. Methods: We examined 883 women (47% Black), aged 18-30 years at enrollment in 1985-1986 (baseline) in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Women selected for this analysis delivered 1 or more live births (total of 1,572 births) during the 20-year follow-up, reported GDM status for pregnancies, had no history of heart disease, and had common carotid intima media thickness (maximum ccIMT; average of the maximum wall thickness of the respective carotid artery segment based on 4 ultrasonic measurements for the common carotid arteries) obtained after 20 years of follow-up in 2005–2006. Results: We classified 121 (14%) women as GDM, and 762 women as non-GDM. Among GDM and non-GDM groups, average age at last birth was 31 years, and average age at the year 20 exam was 44 years. Multivariable linear regression models estimated mean (95%CI) ccIMT (mm) among GDM and non-GDM groups adjusted for baseline parity and follow-up covariates including number of post-baseline births, smoking, education, hypertension status, lipid-lowering medication use, and menopausal status. Unadjusted and fully adjusted mean ccIMT was higher for GDM versus non-GDM groups: (0.791 vs 0.758; p=0.002), and (0.813 vs 0.787;p=0.011), respectively. Adjustment for baseline BMI (a mediator of both GDM and IMT), modestly attenuated the difference in ccIMT means between GDM (0.799) and non-GDM (0.781); p=0.084. Race and age did not act as confounders or as effect modifiers of associations, and BMI was not an effect modifier. Addition of weight gain, and pregnancy-related hypertension during 20 years of follow-up in separate models had little impact on these findings. Conclusions: Among women of reproductive age, GDM during pregnancy may unmask future risk of subclinical atherosclerosis during midlife. Development of GDM during pregnancy serves as an important harbinger of future cardiometabolic diseases in young women long before disease onset.
Abstract MP066: The Role of Environmental Factors in Modifying Heritability of Coronary Heart Disease
Authors: Ci SONG, Zheng Chang, Patrik Magnusson, Erik Ingelsson, Nancy L Pedersen
Journal: Circulation (2012)

Introduction Coronary heart disease (CHD) is affected by both genetic and environmental factors. These classes of factors may act independently or interactively (gene-environment interactions). Recent large genome-wide association (GWA) studies have identified several genetic loci associated with CHD. However, few studies have considered the modifying effects of specific environmental factors on these associations, and the full extent of how those environmental factors affect the additive genetic component of CHD is not known. Hypothesis Our hypothesis was that modifiable environmental factors including smoking, alcohol intake, physical activity and body mass index (BMI) would affect CHD risk via interactions with genetic factors. Methods The environmental factors studied were smoking (ever regular smoker, never regular smoker); alcohol intake (never-drinking, drinking); physical activity (sedentary vs. non-sedentary); and highest BMI during life time (normal [less than 25 kg/m 2 ], overweight [25 to 30 kg/m 2 ], and obesity [more than 30 kg/m 2 ]). All same-sex twins born before 1958 in the Swedish Twin Registry were included in the current study. We identified 6,133 incident CHD events as the first CHD onset without any prior myocardial infarction, stroke or heart failure. We estimated heritability of CHD conditioned on the above-mentioned environmental factors in up to 26,901 twin pairs with environmental information available. Parameter estimation and model fitting was conducted with structural equation modeling as implemented in the software package Mx. Preliminary results The overall heritability of CHD in our sample was 36% (adjusted for age and sex). Smoking and overweight/obesity significantly modified the additive genetic component of CHD (P&lt;0.001 and P=0.038, respectively). Thus, heritability of CHD differed between smokers (29.0%) and non-smokers (42.5%). Further, heritability of CHD also differed among different categories of BMI: 29.9% among normal-weight, 27.1% among overweight and 23.6% among obese individuals. Neither alcohol consumption nor physical activity had any significant modifying effect on heritability of CHD (P=0.33 and 0.16, respectively) Conclusion In our nation-wide twin study of 26,901 twin pairs, purported measures of the environment affected heritability of CHD incidence. We demonstrated that smoking, as well as overweight and obesity modify heritability estimates, potentially indicating that genetic factors play a more prominent role for disease development in the absence of important environmental factors. Our results suggest that increased understanding of gene-environment interactions will be important for full understanding of the etiology of CHD.
Heart Cell Transplantation Improves Heart Function in Dilated Cardiomyopathic Hamsters
Authors: Kyung-Jong Yoo, Ren-Ke Li, Richard D. Weisel, Donald A. G. Mickle, Zhi-Qiang Jia, Eung-Joong Kim, Shinji Tomita, Terrance M. Yau
Journal: Circulation (2000)

Background —Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium. This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. Methods and Results —Ventricular heart cells were isolated from 4-week-old BIO 53.58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4×10 6 cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, n=12 each). Sham-operated hamsters (n=12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater ( P &lt;0.001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915±253 versus control 453±120 and sham 530±187 mm Hg/s, P &lt;0.001, balloon volume of 15 μL). No differences in ventricular function were found between control and sham-operated hamsters. Conclusions —The transplanted ventricular heart cells formed cardiac-like tissue in cardiomyopathic myocardium and improved its contractile function.
Vesnarinone Restores Contractility and Calcium Handling in Early Endotoxemia
Authors: Koh Takeuchi, Pedro J. del Nido, Dimitrios N. Poutias, Douglas B. Cowan, Mamoru Munakata, Francis X. McGowan
Journal: Circulation (2000)

Background —Endotoxin (lipopolysaccharide, LPS) is a trigger of the systemic inflammatory response. We have previously found that vesnarinone and amrinone, when given before LPS, prevented cytokine production and LPS-related cardiac dysfunction. We tested the hypothesis that vesnarinone would improve intracellular Ca 2+ handling and calcium-activated contractile force after the onset of endotoxemia. Methods and Results —Adult rabbits received a bolus injection of LPS or vehicle. Vesnarinone (3 mg/kg) was given intravenously 90 minutes later. Two hours after LPS administration, hearts were perfused in the isolated Langendorff mode. Peak left ventricular developed pressure, ±dp/dt, oxygen consumption (MV̇ o 2 ), and rate×pressure product were evaluated in conjunction with fluorescent spectroscopic determinations of intracellular calcium concentrations (Ca i ) and the rate of Ca i transient decline during diastole (τCa). Peak left ventricular developed pressure and ±dp/dt were significantly lower in the LPS group. These were completely restored by vesnarinone. There was significantly slower diastolic calcium removal (increased τCa) in LPS hearts that was also corrected by vesnarinone; however, the cytosolic calcium overload characteristic of LPS hearts was only partially improved. Reduced mechanical inefficiency (the ratio of rate-pressure product to MV̇ o 2 ) and myofilament sensitivity to Ca i were also significantly improved by vesnarinone. Conclusions —Acute endotoxemia caused contractile protein calcium insensitivity, oxygen wastage, and abnormal calcium cycling. Vesnarinone, given in the rescue mode, normalized LPS-induced myocardial dysfunction and partially restored abnormal calcium cycling. Although the mechanisms responsible for these effects require further clarification, it appears that agents such as vesnarinone may be useful to treat inflammatory-induced myocardial dysfunction.
A deep learning-based electrocardiogram risk score for long term cardiovascular death and disease
Authors: J. Weston Hughes, James Tooley, Jessica Torres Soto, Anna Ostropolets, Tim Poterucha, Matthew Kai Christensen, Neal Yuan, Ben Ehlert, Dhamanpreet Kaur, Guson Kang, Albert Rogers, Sanjiv Narayan, Pierre Elias, David Ouyang, Euan Ashley, James Zou, Marco V. Perez
Journal: npj Digital Medicine (2023)

Abstract The electrocardiogram (ECG) is the most frequently performed cardiovascular diagnostic test, but it is unclear how much information resting ECGs contain about long term cardiovascular risk. Here we report that a deep convolutional neural network can accurately predict the long-term risk of cardiovascular mortality and disease based on a resting ECG alone. Using a large dataset of resting 12-lead ECGs collected at Stanford University Medical Center, we developed SEER, the Stanford Estimator of Electrocardiogram Risk. SEER predicts 5-year cardiovascular mortality with an area under the receiver operator characteristic curve (AUC) of 0.83 in a held-out test set at Stanford, and with AUCs of 0.78 and 0.83 respectively when independently evaluated at Cedars-Sinai Medical Center and Columbia University Irving Medical Center. SEER predicts 5-year atherosclerotic disease (ASCVD) with an AUC of 0.67, similar to the Pooled Cohort Equations for ASCVD Risk, while being only modestly correlated. When used in conjunction with the Pooled Cohort Equations, SEER accurately reclassified 16% of patients from low to moderate risk, uncovering a group with an actual average 9.9% 10-year ASCVD risk who would not have otherwise been indicated for statin therapy. SEER can also predict several other cardiovascular conditions such as heart failure and atrial fibrillation. Using only lead I of the ECG it predicts 5-year cardiovascular mortality with an AUC of 0.80. SEER, used alongside the Pooled Cohort Equations and other risk tools, can substantially improve cardiovascular risk stratification and aid in medical decision making.
Fatigue recovery and connected factors following paediatric concussion
Authors: Fabian Fabiano, Michael Takagi, Nicholas Anderson, Franz E Babl, Silvia Bressan, Cathriona Clarke, Katie Davies, Gavin A Davis, Kevin Dunne, Stephen Hearps, Vera Ignjatovic, Vanessa C Rausa, Marc Seal, Vicki Anderson
Journal: British Journal of Sports Medicine (2023)

Objective Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. Methods 240 children and adolescents aged 5–18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. Results There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p&lt;0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. Conclusion Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.
PLK1 inhibition dampens NLRP3 inflammasome–elicited response in inflammatory disease models
Authors: Marta Baldrighi, Christian Doreth, Yang Li, Xiaohui Zhao, Emily Warner, Hannah Chenoweth, Kamal Kishore, Yagnesh Umrania, David-Paul Minde, Sarah Thome, Xian Yu, Yuning Lu, Alice Knapton, James Harrison, Murray Clarke, Eicke Latz, Guillermo de Cárcer, Marcos Malumbres, Bernhard Ryffel, Clare Bryant, Jinping Liu, Kathryn S. Lilley, Ziad Mallat, Xuan Li
Journal: Journal of Clinical Investigation (2023)

Unabated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis. Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains. Mechanistically, we show that PLK1 orchestrated the microtubule-organizing center (MTOC) structure and NLRP3 subcellular positioning upon inflammasome activation. Treatment with a selective PLK1 kinase inhibitor suppressed IL-1β production in in vivo inflammatory models, including LPS-induced endotoxemia and monosodium urate-induced peritonitis in mice. Our results uncover a role of PLK1 in regulating NLRP3 inflammasome activation during interphase and identify pharmacological inhibition of PLK1 as a potential therapeutic strategy for inflammatory diseases with excessive NLRP3 inflammasome activation.